Effects of Child-Pugh B Cirrhosis on Pharmacokinetics of Tofogliflozin, a New Sodium-Glucose Co-Transporter (SGLT2) Inhibitor.
Journal
Drug research
ISSN: 2194-9387
Titre abrégé: Drug Res (Stuttg)
Pays: Germany
ID NLM: 101602406
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
pubmed:
25
7
2020
medline:
8
6
2021
entrez:
25
7
2020
Statut:
ppublish
Résumé
Tofogliflozin is a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor. A mass balance study with combinations of microdoses revealed that tofogliflozin has high oral bioavailability (97.5%) and that tofogliflozin in circulation is eliminated primarily by metabolic pathways, with the liver playing a prominent role in elimination. This study aimed to evaluate the effect of moderate hepatic impairment on the pharmacokinetics of tofogliflozin and on the pharmacodynamics (urinary glucose excretion [UGE]). In an open-label, parallel-group study, 17 subjects (9 with moderate hepatic impairment [Child-Pugh Class B, score 7-9] and 8 healthy) received a single oral dose of 40 mg tofogliflozin. Plasma and urine concentrations of tofogliflozin were determined. Accumulated UGE, adverse events, and physiological and laboratory test data were monitored. Geometric mean ratio (GMR; geometric mean value for subjects with moderate hepatic impairment / geometric mean value for healthy subjects) of C Moderate hepatic impairment increased C
Sections du résumé
BACKGROUND
BACKGROUND
Tofogliflozin is a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor. A mass balance study with combinations of microdoses revealed that tofogliflozin has high oral bioavailability (97.5%) and that tofogliflozin in circulation is eliminated primarily by metabolic pathways, with the liver playing a prominent role in elimination.
OBJECTIVES
OBJECTIVE
This study aimed to evaluate the effect of moderate hepatic impairment on the pharmacokinetics of tofogliflozin and on the pharmacodynamics (urinary glucose excretion [UGE]).
METHODS
METHODS
In an open-label, parallel-group study, 17 subjects (9 with moderate hepatic impairment [Child-Pugh Class B, score 7-9] and 8 healthy) received a single oral dose of 40 mg tofogliflozin. Plasma and urine concentrations of tofogliflozin were determined. Accumulated UGE, adverse events, and physiological and laboratory test data were monitored.
RESULTS
RESULTS
Geometric mean ratio (GMR; geometric mean value for subjects with moderate hepatic impairment / geometric mean value for healthy subjects) of C
CONCLUSIONS
CONCLUSIONS
Moderate hepatic impairment increased C
Substances chimiques
Benzhydryl Compounds
0
Glucosides
0
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
P8DD8KX4O4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
401-409Informations de copyright
© Georg Thieme Verlag KG Stuttgart · New York.
Déclaration de conflit d'intérêts
4 authors are the employees of Chugai Pharmaceutical Co., Ltd.